Galectin-1 studies in proliferative diabetic retinopathy.

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Abu El-Asrar AM, Ahmad A, Allegaert E, Siddiquei MM, Alam K, Gikandi PW, De Hertogh G, Opdenakker G

Galectin-1 studies in proliferative diabetic retinopathy.

Acta Ophthalmol. 2020 Feb;98(1):e1-e12. doi: 10.1111/aos.14191. Epub 2019 Jul 18.

PubMed ID

31318490 [ View in PubMed

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Abstract

PURPOSE: Galectin-1 regulates endothelial cell function and promotes angiogenesis. We investigated the hypothesis that galectin-1 may be involved in the pathogenesis of proliferative diabetic retinopathy (PDR). METHODS: Vitreous samples from 36 PDR and 20 nondiabetic patients, epiretinal fibrovascular membranes from 13 patients with PDR, rat retinas and human retinal Muller glial cells were studied by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and Western blot analysis. In vitro angiogenesis assays were performed and the adherence of leukocytes to galectin-1-stimulated human retinal microvascular endothelial cells (HRMECs) was assessed. RESULTS: The ELISA analysis revealed that galectin-1 and vascular endothelial growth factor (VEGF) levels were significantly higher in vitreous samples from PDR patients than in those from nondiabetics (p < 0.001 for both comparisons). A significant positive correlation was found between the levels of galectin-1 and VEGF (r = 0.354; p = 0.022). In epiretinal membranes, immunohistochemical analysis showed that galectin-1 was expressed in vascular endothelial cells expressing CD31, myofibroblasts expressing alpha-smooth muscle actin and leukocytes expressing CD45. The galectin-1 receptor neuropilin-1 was expressed on vascular endothelial cells. CD31 staining was used as a marker to assess microvessel density (MVD). Significant positive correlation was detected between MVD in epiretinal membranes and the number of blood vessels expressing galectin-1 (r = 0.848; p < 0.001). Western blot analysis demonstrated significant increase of galectin-1 protein in rat retinas after induction of diabetes. ELISA analysis revealed that hydrogen peroxide and cobalt chloride (CoCl2 ) induced upregulation of galectin-1 in Muller cells. Treatment with galectin-1 induced upregulation of VEGF in Muller cells and increased leukocyte adhesion to HRMECs. The galectin-1 inhibitor OTX008 attenuated VEGF-induced HRMECs migration and CoCl2 -induced upregulation of NF-kappaB, galectin-1 and VEGF in Muller cells. CONCLUSIONS: These results suggest that galectin-1is involved in the pathogenesis of PDR.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
OTX-008	Galectin-1	Protein	Humans	Yes	Inhibitor	Details